Do Atomoxetine and Methylphenidate Differentially Impact Sustained Attention and Inhibitory Control in Individuals With ADHD?

Anne-Claude Bedard, PhD; Jeffrey M. Halperin, PhD; Mark A. Stein, PhD, ABPP; and Jeffrey H. Newcorn, MD
Mount Sinai School of Medicine, New York, New York (Drs Bedard, Halperin, and Newcorn); Queens College of the City University of New York, New York (Dr Halperin); and the University of Illinois at Chicago, Chicago (Dr Stein)

This poster presentation was supported by NIH RO1 MH070935.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that is defined by inattention and hyperactivity/impulsiveness. Although stimulant medication such as methylphenidate (MPH) improves aspects of sustained attention and inhibitory control, it is important to understand how the longer-acting stimulant Concerta (MPH) and nonstimulant atomoxetine (ATX) differentially influence aspects of sustained attention/vigilance, given their wide use for the management of behavior. The objective of this study is to test whether ATX improves objective measures of attention and inhibitory control, given the uncertainty regarding the magnitude of clinical effects of ATX in relation to MPH. It is hypothesized that performance will be improved by both treatments, but there will also be differential response because ATX and MPH work via different neurochemical mechanisms.

Methods: Sixty-one school-aged individuals (48 male) (mean age = 9.7 +/- 2.7 years) with ADHD received MPH (54 +/- 16 mg) and ATX (1.4 +/- 0.4 mg/kg) in a randomized, double-blind, crossover design. Medication was titrated in two 4–6 week treatment blocks separated by a 2-week placebo washout. Cognitive assessments occurred at baseline, following placebo washout, and at the end of each treatment block. Attention and inhibitory control were measured using the Conners’ Continuous Performance Test, which provided age-adjusted scores of reaction time, response consistency, and errors. Repeated measured analyses of variance (ANOVA) with Time (pre-medication, post-medication) and Treatment type (MPH, ATX) entered as within-subject factors were performed.

Results: Both MPH and ATX reduced reaction time (p<0.001), increased consistency of responding (p<0.001) and reduced omission errors (p<0.05). In addition, there was a significant Time x Treatment interaction such that MPH improved response consistency to a greater degree than ATX (p<0.01). Commission errors, response bias (ß), and detectability (d'), did not improve significantly with either treatment.

Conclusions: These data suggest that clinically-observed improvements in attention following treatment with MPH and ATX can be empirically-validated using objective neurocognitive measures. Notably, the stimulant MPH and the non-stimulant ATX appear differentially effective for improving response consistency in individuals with ADHD, and neither treatment significantly improved measures of inhibitory control.

References
Riccio CA, Waldrop JJ, Reynolds CR, et al. Effects of stimulants on the continuous performance test (CPT): implications for CPT use and interpretation. J Neuropsychiatry Clin Neurosci. 2001;13(3):326–335.

Pietrzak RH, Mollica CM, Maruff P, et al. Cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder. Neurosci Biobehav Rev. 2006;30(8):1225–1245.

Conners CK. Conners' CPT II: Continuous Performance Test II Technical Guide and Software Manual. New York: Multi-Health Systems Inc; 2000.

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